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PMID: 2189894 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Double minutes arise from circular extrachromosomal DNA intermediates which integrate into chromosomal sites in human HL-60 leukemia cells.

The Journal of clinical investigation ·Vol. 85 ·No. 6 ·1990-06-00 ·Pages 1887-95

Von Hoff DD, Forseth B, Clare CN, Hansen KL, VanDevanter D

Abstract

Amplification of oncogenes has been found to be an important prognostic factor in behavior of patients' malignancies. In this study we have used new gel electrophoresis techniques to follow the location of amplified c-myc oncogene sequences in HL-60 promyelocytic leukemia cells. In passages 46-62 of the cells, the cells contain amplified c-myc sequences on submicroscopic circular extrachromosomal DNA (episomes). With increased passages in culture (passages 63-72) the cells lose the episome c-myc sequences with a shift of those sequences to double minutes. With additional passage in culture, the c-myc shifts from the double minutes to a chromosomal site der(5)t(5;17)(q11.2;q?11.2). Concomitant with the shift of the c-myc sequences into the chromosomal compartment is a phenotypic change of a shortened cell-doubling time. These studies provide the first molecular evidence of a progression from a submicroscopic location for amplified oncogene sequences to a chromosomal location for the amplified sequences. This molecularly documented model can now be used to test various strategies to prevent incorporation of extrachromosomally located oncogene sequences into chromosomal sites. Prevention of integration of the oncogene sequences into chromosomal sites could modulate progression of patients' tumors.

MeSH Terms
Cell Division Chromosome Aberrations DNA, Neoplasm/genetics Gene Amplification Humans Leukemia, Promyelocytic, Acute/genetics,pathology Nucleic Acid Hybridization Oncogenes Plasmids Proto-Oncogene Proteins/genetics Proto-Oncogene Proteins c-myc Tumor Cells, Cultured
Chemicals
DNA, Neoplasm Proto-Oncogene Proteins Proto-Oncogene Proteins c-myc
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Von Hoff D D
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7884.
Forseth B
Clare C N
Hansen K L
VanDevanter D
References (44)
44 references, click to expand
  1. Banded karyotypes from bone marrow: a clinical useful approach.
    Hum Genet. 1980 Feb;53(2):205-9 PMID: 7358387
  2. Chromosomes of human cancer cells.
    Br Med J. 1962 Dec 1;2(5317):1431-5 PMID: 13978541
  3. Chromosome abnormalities associated with salivary gland epithelial cell lines transformed in vitro and in vivo with evidence of a role for genetic imbalance in transformation.
    Cancer Res. 1981 Apr;41(4):1508-17 PMID: 6260341
  4. Chromosomal and extrachromosomal localization of amplified dihydrofolate reductase genes in cultured mammalian cells.
    Cold Spring Harb Symp Quant Biol. 1981;45 Pt 2:785-97 PMID: 6942951
  5. Double minutes in human tumor cells.
    Cancer Genet Cytogenet. 1982 Feb;5(1):81-94 PMID: 6175392
  6. Amplified DNA sequences in Y1 mouse adrenal tumor cells: association with double minutes and localization to a homogeneously staining chromosomal region.
    Proc Natl Acad Sci U S A. 1982 Mar;79(5):1597-601 PMID: 6951198
  7. Amplification of endogenous myc-related DNA sequences in a human myeloid leukaemia cell line.
    Nature. 1982 Aug 12;298(5875):679-81 PMID: 6285209
  8. Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells.
    Proc Natl Acad Sci U S A. 1982 Dec;79(24):7824-7 PMID: 6961453
  9. Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells.
    Proc Natl Acad Sci U S A. 1982 Dec;79(24):7837-41 PMID: 6818551
  10. Two human c-onc genes are located on the long arm of chromosome 8.
    Proc Natl Acad Sci U S A. 1982 Dec;79(24):7842-6 PMID: 6961456
  11. Double minutes and homogeneously staining regions: gene amplification in mammalian cells.
    Annu Rev Genet. 1982;16:21-59 PMID: 6760799
  12. Association of amplified oncogene c-myc with an abnormally banded chromosome 8 in a human leukaemia cell line.
    Nature. 1983 Dec 1-7;306(5942):494-7 PMID: 6580529
  13. Evidence for selection of homogeneously staining regions in a human melanoma cell line.
    Cancer Res. 1984 Jan;44(1):233-7 PMID: 6197160
  14. Loss of unstably amplified dihydrofolate reductase genes from mouse cells is greatly accelerated by hydroxyurea.
    Proc Natl Acad Sci U S A. 1983 Dec;80(24):7533-7 PMID: 6584871
  15. Gene amplification, drug resistance, and cancer.
    Cancer Res. 1984 May;44(5):1735-42 PMID: 6713376
  16. Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage.
    Science. 1984 Jun 8;224(4653):1121-4 PMID: 6719137
  17. Hybridization of nucleic acids immobilized on solid supports.
    Anal Biochem. 1984 May 1;138(2):267-84 PMID: 6204550
  18. Gene amplification in cultured animal cells.
    Cell. 1984 Jul;37(3):705-13 PMID: 6378386
  19. Gene amplification.
    Annu Rev Biochem. 1984;53:447-91 PMID: 6383198
  20. Oncogene mobility in a human leukemia line HL-60.
    Cancer Genet Cytogenet. 1985 Jun;17(2):133-41 PMID: 3857965
  21. Cytogenetic analysis using quantitative, high-sensitivity, fluorescence hybridization.
    Proc Natl Acad Sci U S A. 1986 May;83(9):2934-8 PMID: 3458254
  22. Oncogene amplification in tumor cells.
    Adv Cancer Res. 1986;47:235-81 PMID: 3022564
  23. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.
    Science. 1987 Jan 9;235(4785):177-82 PMID: 3798106
  24. Novel submicroscopic extrachromosomal elements containing amplified genes in human cells.
    Nature. 1987 Jun 4-10;327(6121):434-7 PMID: 3587364
  25. DNA amplification in drug resistant cells and in tumours.
    Cancer Surv. 1986;5(1):1-23 PMID: 3297310
  26. Characterization of an episome produced in hamster cells that amplify a transfected CAD gene at high frequency: functional evidence for a mammalian replication origin.
    Mol Cell Biol. 1987 May;7(5):1740-50 PMID: 2885742
  27. Amplification of the c-myc oncogene is associated with an abnormally banded region on chromosome 8 or double minute chromosomes in two HL-60 human leukemia sublines.
    Cancer Genet Cytogenet. 1987 Sep;28(1):127-35 PMID: 3475162
  28. Double minute chromosomes can be produced from precursors derived from a chromosomal deletion.
    Mol Cell Biol. 1988 Apr;8(4):1525-33 PMID: 2898098
  29. Circular DNA of 3T6R50 double minute chromosomes.
    Nucleic Acids Res. 1988 Jun 10;16(11):4841-51 PMID: 3290843
  30. Metaphase chromosome anomaly: association with drug resistance and cell-specific products.
    Science. 1976 Jan 16;191(4223):185-7 PMID: 942798
  31. A novel chromosome abnormality in human neuroblastoma and antifolate-resistant Chinese hamster cell lives in culture.
    J Natl Cancer Inst. 1976 Sep;57(3):683-95 PMID: 62055
  32. Double minute chromosomes and the homogeneously staining regions in chromosomes of a human neuroblastoma cell line.
    Science. 1977 Nov 18;198(4318):739-41 PMID: 71759
  33. Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture.
    Nature. 1977 Nov 24;270(5635):347-9 PMID: 271272
  34. A new chromosome type replacing the double minutes in a mouse tumor.
    Cytogenet Cell Genet. 1978;20(1-6):12-23 PMID: 77207
  35. Gene amplification and drug resistance in cultured murine cells.
    Science. 1978 Dec 8;202(4372):1051-5 PMID: 715457
  36. Characterization of the continuous, differentiating myeloid cell line (HL-60) from a patient with acute promyelocytic leukemia.
    Blood. 1979 Sep;54(3):713-33 PMID: 288488
  37. Cell lines from human colon carcinoma with unusual cell products, double minutes, and homogeneously staining regions.
    Cancer Res. 1979 Dec;39(12):4914-24 PMID: 498117
  38. Amplified human MYC oncogenes localized to replicating submicroscopic circular DNA molecules.
    Proc Natl Acad Sci U S A. 1988 Jul;85(13):4804-8 PMID: 3164477
  39. Pulsed-field gel electrophoresis of very large DNA molecules.
    Annu Rev Biophys Biophys Chem. 1988;17:287-304 PMID: 3293589
  40. The importance of circular DNA in mammalian gene amplification.
    Cancer Res. 1989 Mar 15;49(6):1333-40 PMID: 2647287
  41. Autonomously replicating episomes contain mdr1 genes in a multidrug-resistant human cell line.
    Mol Cell Biol. 1989 Jan;9(1):109-15 PMID: 2648129
  42. Pulsed field gel electrophoresis.
    Biotechniques. 1989 Jan;7(1):34-42 PMID: 2698185
  43. Simple construction of rubber-based agarose block molds for pulsed-field electrophoresis.
    Biotechniques. 1989 Feb;7(2):143-4 PMID: 2629844
  44. A new chromosome region possibly derived from double minutes in an in vitro transformed epithelial cell line.
    Cytogenet Cell Genet. 1980;27(1):2-7 PMID: 7389416
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI114650
Published
1990-06-00
Pages
1887-95
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC296655
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI114650 PMC Full Text View journal details
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